Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

Chronic pain occurs with greater frequency in women, with a parallel sexually dimorphic trend reported in sufferers of many autoimmune diseases. There is a need to continue examining neuro-immune-endocrine crosstalk in the context of sexual dimorphisms in chronic pain. Several phenomena in particular need to be further explored. In patients, autoantibodies to neural antigens have been associated with sensory pathway hyper-excitability, and the role of self-antigens released by damaged nerves remains to be defined. In addition, specific immune cells release pro-nociceptive cytokines that directly influence neural firing, while T lymphocytes activated by specific antigens secrete factors that either support nerve repair or exacerbate the damage. Modulating specific immune cell populations could therefore be a means to promote nerve recovery, with sex-specific outcomes. Understanding biological sex differences that maintain, or fail to maintain, neuroimmune homeostasis may inform the selection of sex-specific treatment regimens, improving chronic pain management by rebalancing neuroimmune feedback. Given the significance of interactions between nerves and immune cells in the generation and maintenance of neuropathic pain, this review focuses on sex differences and possible links with persistent autoimmune activity using sciatica as an example.